Severe esophagitis directly induced by accumulation of crizotinib-residue at the esophageal mucosa proven with polarizing microscope examination

抄録

Crizotinib demonstrates dramatic effects for the patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase gene (ALK) fusion or c-ros oncogene 1 (ROS-1) fusion-positive lung cancer, with some characteristic　toxicities. Although several studies reported that serious esophagitis was induced by crizotinib, the detailed mechanisms　and ways to ameliorate the esophagitis have not been clarified. In this report, we report two cases with lung cancer who had been treated with crizotinib and developed severe esophagitis. Polarizing microscope examination clearly revealed that the accumulation of crizotinib-residue in the esophageal biopsy samples at the second anatomical narrowing of the esophagus in both cases. Since it seemed that the accumulation of crizotinib-residue in the esophageal mucosa directly caused the esophageal inflammation, we recommended taking crizotinib with a large amount of water (more than 200 ml) and to stay sitting upright for 30 minutes after intake. After that, the esophagitis gradually improved and the patients could continue taking crizotinib without dose reduction or withdrawal. Our experiences suggest that this crizotinib-induced esophagitis could be easily prevented by proper administration of crizotinib.